TI - Neurabin Regulates Synaptic Transmission . AB - Function of AMPA receptor is modulated by different mechanisms , including PHOSphorylation and their membrane expression [8] , [9] . In this report , we found that AMPA receptor -mediated EPSC is significantly increased in the neurabin KO mice . At least three possibilities may account for the enhancement . First , the expression of AMPA receptor may be upregulated in neurabin KO mice . This possibility is excluded , since the total expression of GluR1 or GluR2&3 in hippocampus is similar between wild-type and neurabin KO mice . However , the results may reflect a preferential synaptic expression of AMPARs in the neurabin KO mice . Second , presynaptic glutamate release may be increased in the KO mice . However , this is not the case , as we found that PPF is increased in KO mice , suggesting the release probability may be decreased in KO mice . Third , the PHOSphorylation of AMPA receptor may be altered in neurabin KO mice . Indeed , our biochemical results showed that phosphorylaTION of GluR1 is significantly decreased at PKA site (Ser845) , whereas PHOSphorylation is unaltered at the CaMKII site (Ser831) . The results are particularly interesting , considering the both sites could be regulated by PP1 [9] , [12] . One possible explanation for the results is that neurabin-binding protein PP1 may not directly target the phosphorylaTED sites on GluR1 subunit in dendritic spines , but through other SUBstrates instead . For instance , PP1 could inhibit CaMKII function [15] , [33] , thereby affecting the PHOSphorylation on GluR1p831 . Recently , it has been reported that PHOSphorylation of GluR1p845 in the neostriatum was reduced in neurabin KO mice [20] . The amplitude of mEPSC , which reflects the function of postsynaptic AMPA receptor , however , is not altered in neostriatal slices [20] . In contrast , it was found that acute expression of neurabin deletion mutant decreases mEPSC amplitude in cultured hippocampal slice [25] , [34] . The reason for the discrepancy may reside in : (1) Hippocampal cultured neurons/slices may represent functions of neurabin in early developmental stages . The present studies were performed from adult hippocampal slices . (2) Inhibition of neurabin stimulated motility and the number of dendritic spines [34] . The possibly reduced spine size may lead to the decreased responses of single synaptic event . However , the increased spine density and synapses may keep the synaptic input constant [34] or increased as shown in the present study . (3) The discrepancy of evoked EPSCs and mEPSC observed in neurabin KO mice could be reconciled since evoked response and spontaneous response may recruit different presynaptic release pools [35] as well as the postsynaptic receptor pools ( Kavalali E , personal communication ) .